MKT Wpr229 EU GMP Annex 15 Qualification and Validation

White Paper
EU GMP Guide-Annex 15
Qualification & Validation draft
released
In February 2014, a draft of the revised Annex 15 was released by the European
Commission (EC) for public comment. The draft version is based on an EMA Concept
Paper, published in November 2012 which outlined various reasons for the revision of
Annex 15.
The changes to the Annex are quite extensive and this White Paper discusses the
proposed revision in detail.
2014 PharmOut. This document has been prepared solely for the use of PharmOut and its clients. Copying is
prohibited.
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EU GMP Guide-Annex 15 Qualification & Validation draft released
Introduction:
The current version of Annex 15 of the EU Guide to GMP was originally published in
September 2001, and since then there have been significant changes in the GMP
environment. The EMA is in the process of updating its guideline on Process Validation
(a draft version is currently available), and there have been advancements in
manufacturing technology and continuous manufacture processes. There has also
been many changes to other Chapters and Annexes in the EU GMP guide, which have
an impact on Annex 15, and therefore the revision of this Annex is required. Also the
current version of the US FDA Guide on Process Validation, as well as the approaches
in ASTM E2500-07 Standard Guide for Specification, Design, and Verification of
Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment may
have also justified the change.
Who is affected by the changes?

Manufacturers may be directly affected by the changes if they sell the following
categories of products into EMA regulated markets once the Annex is revised and
effective:
Human drugs
Veterinary drugs
Biological and biotechnology products
Active pharmaceutical ingredient (API) manufacturers
Medical devices manufacturers are not directly affected; however, the guidance may
contain useful information for qualification and validation activities.
Manufacturers in other non-EU PIC/S regulated markets are likely to be affected
indirectly. The close alignment of EU and PIC/S means that PIC/S may adopt the
guidance in full, or develop its own guidance based on the EU document.
What are the key changes in the new guidance?

The key change in the draft is the inclusion of the principles of ICH Q8, Q9, Q10 and Q11
(see Figure 1 below). These principles allow the use of concepts such as knowledge
management (ICH Q8 & Q10) and science and risk-based approaches (ICH Q9) to
support lifecycle validation & qualification activities, and the use of a design space (ICH
Q8) for Process Validation.
prohibited.
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Figure 1: ICH Q8, Q9, Q10 & Q11.
Other major changes within the draft are detailed in the list below, some of which will
be discussed in greater detail later:
Cross-reference made to Annex 11 Computerised systems

Planning and documentation for Qualification and Validation
Added information on the qualification stages for equipment, facilities and
utilities
Major revision of the Process and Cleaning Validation and sections
New sections added on:
o Ongoing Process Verification during Lifecycle
o Verification of Transportation
o Validation of Packaging
o Qualification of Utilities
o Validation of Test Methods
Planning and documentation for Qualification &

Validation
During the planning phase, it is now expected that all stages of the lifecycle for
equipment, facilities, systems and processes /products need to be taken into
consideration. In terms of organisation during qualification and validation, the draft
indicates that the Pharmaceutical Quality System (PQS) should define the Validation
staff requirements (suitably trained to follow procedures) and the responsibility for
oversight over the whole validation lifecycle, in alignment with Chapter 1 of the EU
GMP Guide. The Annex indicates that this responsibility (including validation document
approval) may not necessarily be a quality management or quality assurance function,
but needs to be appropriate over the whole validation lifecycle. This shift in
appropriate oversight aligns with the thinking in ASTM E2500, which does not
mention responsibilities for someone within a quality function, but instead allows for
Subject Matter Experts (SMEs) to confirm acceptance of verification and release of
the manufacturing systems, authorising fitness for its intended use.
prohibited.
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The draft still states that the Validation Master Plan (VMP) should define the key
elements of the validation program but now should also contain the "current validation
status" of "facilities, systems, equipment and processes" and also define the ongoing
validation strategy, including requalification/revalidation. It does not mention utilities,
but may be assumed under "systems". The VMP should now also cross-reference the
template formats used for protocols and reports, as well as assessment of resources
required for the entire project. The VMP should also summarise how acceptance
criteria will be handled and provide clarity on deviation management during validation.
To align with the lifecycle approach, the VMP should confirm that materials used for
validation are of sufficient quality and obtained from appropriately qualified
suppliers.
Assessment of risk:
As part of the alignment with ICH Q9, a well-documented quality risk management
approach should be used to justify validation activities. As knowledge and
understanding increases during the project phase and during commercial
manufacture, the risk assessments should be repeated as required, with changes
clearly documented and their impact understood.
Third Party Documents

The Documentation section of the draft outlines the importance of Good Documentation
Practice (GDP) for knowledge management throughout the validation lifecycle. For
complex projects, the inter-relationships between documents should be understood
and visible and in particular, when third party documents are used, they must be
suitable and compliant with company procedures before approval.
Handling Changes and Deviations

The instruction for the handling of protocols (pre and post execution) and reports has
been refined. Protocols should now also include definitions of "critical systems,
attributes and parameters which are important", along with their acceptance criteria.
Section 2.6 states that "Any changes to the approved protocol during execution should
be documented as a deviation and be scientifically justified." The Annex does not detail
what types of "changes" could be defined as a "deviations". For example, obvious
typographical errors that have no impact on protocol execution may require a change,
but may not necessarily warrant a deviation. This should be dependent on the
manufacturers own PQS.
The Approval Process

The Annex also now clearly states that the qualification and/or validation report should
summarise the results obtained "against the acceptance criteria. Also, any subsequent
changes to the acceptance criteria should be scientifically justified with a final
prohibited.
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recommendation on the outcome of the study detailed in the report. The formal
release for the next step in the validation process is still evident, and can be part of the
approval of the validation report or separate summary document authorised by the
relevant responsible personnel. Section 2.9 now also states that where "certain
acceptance criteria or deviations have not been fully addressed", with a documented
assessment, "conditional approval" can be given to proceed to the next validation
stage, provided that there is "no significant impact" upon the next stage by doing so.
Qualification stages for equipment, facilities and

utilities
As part of the alignment with ICH Q8 to Q11, the activities undertaken during
qualification and validation should "consider all stages from initial development of the
user requirements specification or initial process development through to the end of

use of the equipment, facility or process." This section goes on to suggest some of the
stages and criteria that could be used, but it may depend on the individual project
circumstances and may be different. This may allow for the implementation of other
qualification and validation approaches such as ASTM E2500. The suggested stages
are summarised briefly below.
Figure 2: Possible qualification and validation stages from the Draft Annex 15.
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User Requirements Specification (URS)

This section is new to Annex 15 and states that "the specification for new facilities,
systems or equipment should be defined in a URS and/or a functional specification"

and is shown by point (a) in Figure 2 above. This is a significant change as the current
version of Annex 15 does not mention a specification phase. The URS should be written
with quality elements in mind, as well as minimising GMP risks and "should be a point
of reference throughout the validation life cycle". It does not state that a URS should be
written for the process itself, and there is no reference to the benefits/use of other
types of specifications generally used within the industry.
Design qualification (DQ)

The current version of Annex 15 indicates that Design Qualification (DQ) could be the
first element for the validation of new facilities, systems or equipment. The draft
version indicates that the next element is DQ which serves to ensure the compliance
of the design with GMP and should be demonstrated and documented. It also states
that the requirements of the user requirements specification should also be verified
during the design qualification, but does not mention the Functional Specification, or
indeed other specification such as design specifications. This section could also have
adopted a lifecycle approach to design qualification preceding design reviews, with the
same intent as described in ASTM E2500-07:
Design reviewsplanned and systematic reviews of specifications, design, and design

development and continuous improvement changes performed as appropriate
throughout the life-cycle of the manufacturing system. Design reviews evaluate
deliverables against standards and requirements, identify problems, and propose
required corrective actions.
Factory acceptance testing (FAT) /Site acceptance testing (SAT)

The draft Annex now contains a new section on Factory Acceptance Testing (FAT) and
Site Acceptance Testing (SAT) of equipment only as shown in (b) in Figure 2 above. The
URS and DQ sections as above refers to facilities systems and equipment, but only
equipment is mentioned in this section. The section recommends the evaluation of
equipment incorporating novel or complex technology at the vendors site before
delivery, and that equipment should be demonstrated to be in compliance with the
URS/functional specification, unless otherwise justified. Testing and documentation
reviews carried out during the FAT may not need to be repeated once delivered on site
if transport and installation has no impact. The appropriateness of carrying out more
testing or not should be assessed and documented.
Installation qualification (IQ)

The definitions and expectations of Installation Qualification (IQ) are the same in both
versions of Annex 15, but the new draft also states that the installation should be " as
prohibited.
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detailed in the design and confirmation of current engineering regarding drawings and
specifications" and the IQ must include "verification of the correct installation against
pre-defined criteria". This is an obvious requirement for any protocol, but is not evident
from the current version of Annex 15.
Operational qualification (OQ)

The OQ section in the draft now details that depending on the complexity of the
equipment, a combined IQ/OQ may be performed. It does not state that the same is true
for facilities, systems, utilities and/or processes. The draft no longer states that the
completion of a successful OQ permits the formal release of the facilities, systems
and equipment, but it can be inferred from point 2.9 of the draft that this approach is
acceptable.
Performance qualification (PQ)

For Performance Qualification (PQ), the draft allows for the qualification activities to be
performed in conjunction with OQ or Process Validation. Section 3.14 now details what
a PQ "could" include instead of what it "should" include, as per the current version of
Annex 15. Sampling and testing used to confirm process control should encompass
what has been previously developed from knowledge of the process and the facilities,
systems or equipment and justified. The tests should cover the process operating
range "unless documented evidence from the development phases which confirm the
operational ranges are available".
It is important to note that the definition of Performance Qualification is somewhat
different within the current PIC/S document PI 006-3 that covers recommendations on
VMP, IQ and QO, Non-sterile Process Validation and Cleaning Validation. It includes a
definition for Process Validation, but states that the term Performance Qualification or
PQ may be used also. There is also potential for confusion using the abbreviation PQ
within industry as the US FDA Process Validation Guidance defines PQ as Process
Qualification which has two elements:. (1) is the design of the facility and qualification
of the equipment and utilities and (2) is the process performance qualification (PPQ).
which combines the actual facility, utilities, equipment (each now qualified), and the
trained personnel with the commercial manufacturing process, control
procedures, and components to produce commercial batches, and will confirm the
process design and demonstrate that the commercial manufacturing process
performs as expected.
Process Validation
The requirements and principles outlined in this section are still applicable to the
manufacture of all pharmaceutical dosage forms, and now also cover site transfers
and ongoing process verification. The Annex should be used in conjunction with the
EMA guideline on Process Validation, (currently in draft) which provides direction on
what is required for regulatory submission and GMP requirements. A White Paper on
prohibited.
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the EMA Draft Guidance can be found on the PharmOut website, and a summary of the
main sections of the EMA PV Guide are shown in Figure 3 below. Note that
Retrospective Validation is not mentioned in the draft, nor is it mentioned in the draft
EMA PV Guide. It is assumed that all validation will be either prospective or concurrent
in exceptional circumstances.
Figure 3: Process Validation approaches from the Draft Annex 15.

The Draft of Annex 15 has sub-headings with descriptions on Concurrent Validation,
the Traditional Approach, Continuous Process Verification and Ongoing Process
Verification. The only information on the Hybrid Approach is in section 4.24 where it
states that A hybrid approach using the traditional approach and continuous process
verification for different production steps can also be used, and a definition is missing
from the Glossary. Within the draft, the terms Ongoing Process Verification and
Continuous Process Verification are used and are further described below. Both
terms are described as being the same in the Glossary, but this may lead to confusion.
Section 4.3 states that products may be developed using a traditional approach or a
continuous verification approach but again, does not mention the hybrid approach
here. It goes on to say that however irrespective of the approach used, processes
must be shown to be robust and ensure consistent product quality before any product
is released to the market. Manufacturing processes should undergo a prospective
validation programme wherever possible prior to marketing of the product.
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A lifecycle approach is applied linking product and

process development, validation of the commercial
manufacturing process and maintenance of the process
in a state of control during commercial production
Process Validation should be based on documented critical process parameters
(CPPs) and critical quality attributes (CQAs) as a result of risk assessment activities
as applicable. If a design space justification is used, the process knowledge and
statistics used to confirm a state of control should be available. Validation batches
(including continuous process verification) that are released to the market should fully
comply with GMP & Marketing Authorisation and meet all validation acceptance
criteria.
The draft also indicates that the number of validation batches could be reduced by the
use of a bracketing approach for products which are transferred to another/within site
where sufficient product knowledge exists, and if a continuous manufacturing process
is used, the batch size for Process Validation should be justified. The options for
Process Validation are discussed briefly below.
Concurrent validation
The draft Annex indicates that concurrent validation may be acceptable in exceptional
circumstances "where there is a strong risk benefit to the patient" but the decision
must be justified and documented in the VMP and approved by authorised personnel.
The current US FDA Process Validation Guidance document provides greater detail on
the potential benefits to concurrent validation. It indicates that concurrent release
might be appropriate for processes used infrequently for various reasons including
limited demand drugs, radiopharmaceuticals with short half-lives or drugs that are
medically necessary and are being manufactured in coordination with the Agency (US
FDA) to alleviate a short supply.
Traditional approach to validation

The "traditional approach" allows the manufacturer to produce a number of batches
under routine conditions, confirming reproducibility. The number of batches predefined and the sampling to be undertaken must be justified based on QRM principles
to demonstrate "a high level of assurance that the process is capable of consistently
delivering quality product". The section also goes on to say that a minimum of three
batches may be justifiable, but the validation exercise may be supplemented with data
from "subsequent batches as part of an on-going process verification exercise.
prohibited.
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Continuous Process Verification

CPV can be used for products that have been developed by a quality by design approach
as an alternative to traditional process validation, as discussed above. CPV should be
based on a "science based control strategy for the required attributes for incoming
materials, critical quality attributes and critical process parameters to confirm product
realisation". This should also include regular evaluation of the control strategy and the
use of statistical tools and Process Analytical Technology (PAT) may be used. The
number of batches used to justify that the process is consistent and capable must be
justified. CPV can also be used after changes or during ongoing process verification
even if the process was initially validated using the traditional approach, but a
substantial amount of product and process knowledge must have been gained from
experience and historical data first, and again justified.
A Hybrid Approach using the Traditional Approach and Continuous Process
Verification together for different production steps can also be used, but there is little
detail on the Traditional Approach here.
Ongoing Process Verification during Lifecycle

Ongoing process verification is required periodically to ensure that a state of control is
maintained throughout the product lifecycle. The period of the verification should be
based on the level of process understanding and process performance at all times
during the product lifecycle. This ongoing verification should be used to support the
Product Quality Review and should be conducted under an approved protocol with a
report, using statistical tools to support conclusions made. The report should contain a
detailed assessment of the variability and capability of the process and ensure a state
of control. It should also assess changes during the product lifecycle and their impact
on the validated state of the process.
Cleaning validation
Within the Glossary of the draft, the definition for Cleaning Validation has changed from
"will provide equipment which is suitable for processing medicinal products" to "will
remove all traces of the previous product used in the equipment." This statement is
weaker than the older definition as it only infers that previous product be removed and
not potential contamination such as bioburden and endotoxin that might be present.
The draft identifies that visually clean is an important part of cleaning validation but
not acceptable acceptance criteria on its own. The Annex identifies that cleaning
validation may take some time to complete and that "ongoing verification" after each
batch may be required for a period of time to gather sufficient data.
Section 9.5 states that the "Limits for the carry-over of product residues should be
based on a toxicological evaluation to determine the product specific permitted daily

prohibited.
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exposure (PDE) value" and should be documented in a risk assessment. This is not
particularly helpful for non-toxic products/administration routes.
The PDE represents a dose that is unlikely to cause an adverse effect if an individual is
exposed at this dose every day for a lifetime. This approach is not new and the PDE
concept is already used in the ICH Guideline Q3C (R4) Guideline for Residual Solvents.
The PDE determination is carried out substance-specific on the basis of all available
toxicological and pharmacological data from clinical, preclinical or toxicological
studies by means of the NOEL (no-observed-effect-level). The NOEL is the highest dose
at which no critical effect is observed. This ties in with EMAs draft guide titled
Guideline on setting health based exposure limits for use in risk identification in the
manufacture of different medicinal products in shared facilities released in December
2012. The acceptance criteria should also consider the "potential cumulative effect of
multiple equipment in the process equipment train". The assessment for potential
microbial and endotoxin contamination should also be assessed as applicable, along
with the influence of dirty and clean hold times for equipment.
Section 9.8 states that "where a worst case product approach is used as a cleaning
validation model, the rationale for selection of the worst case product should be
justified and the impact of new products to the site assessed" and "when there is no
single worst case product when using multi-purpose equipment, the choice of worst
cases should consider toxicity and PDE value as well as solubility. Worst case cleaning
validation should be performed for each cleaning method used".
Typically, the cleaning procedure should be performed

an appropriate number of times based on a risk
assessment and meet the acceptance criteria in order to
prove that the cleaning method is validated
The Annex no longer looks for three consecutive batches to demonstrate that the
cleaning process is validated. It now states that cleaning process be carried out an
appropriate number of times based on a risk assessment.
Cleaning verification may be used instead (but principles still based on the principles in
the Cleaning Validation section of the Annex) of cleaning validation when
manufacturing batches infrequently or for investigational medicinal products. If
cleaning validation has been proven to be ineffective/not appropriate for some
equipment, then dedicated equipment should be used for each product.
prohibited.
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New Sections
Ongoing Process Verification during Lifecycle
This section has been discussed in the Process Validation section above.
Verification of Transportation
Verification of transportation ensures product(s) and samples are transported in
accordance with the conditions defined in the Marketing Authorisation, product
specification file or by the manufacturer. Seasonal variations should also be
considered. The Annex states that a risk assessment should be performed to consider
the impact of conditions other than temperature during transport and examples are
given in this section.
Validation of Packaging
Packaging should be validated as variation in equipment processing parameters during
primary packaging may have an impact on the product i.e. blister strips, sachets etc.
Qualification should encompass the entire operating ranges defined for the critical
component parameters.
Qualification of Utilities
The quality of utilities such as water, steam, air, gases etc. should be confirmed
following installation. Extent of qualification should reflect seasonal variation and
intended use. A risk assessment should be carried out to mitigate any risks of failure
and is particularly important for direct product contact systems like Heating Ventilation
Air Conditioning (HVAC) systems.
Validation of Test Methods

Analytical methods (including microbiological methods) used for qualification,
validation or cleaning should be appropriately validated. This section cross references
Chapter 6 of the EU-GMP guide Part I.
8.3 states that where microbial testing of surfaces in clean rooms is carried out,
validation should be performed on the test method to confirm that sanitising agents do
not influence the result.
prohibited.
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Other notable changes within the Annex:

Re-qualification
The "Re-validation" section has been retitled as "Re-qualification" and states that
"Facilities, utilities, systems, equipment should be evaluated at an appropriate
frequency to confirm that they remain in a state of control". Also, "Where additional re-
qualification is necessary and performed at a specific time period, the period should be
justified and, the criteria for evaluation defined. Furthermore the possibility of
incremental changes should be assessed".
Change Control
11.3 of the draft states that "Where design space is used, the impact on changes to the
design space should be considered against the registered design space within the
Marketing Authorisation and the need for any regulatory actions assessed". QRM
should be used to evaluate planned changes and assess their impact and to "avoid
unintended consequences and to plan for any necessary process verification or
requalification efforts". Once the change has been executed, an evaluation of its
effectiveness should be carried out to confirm that the change has been successful.
Glossary
The glossary now contains descriptions of the following terms new to the draft:
Bracketing approach
Continuous process verification
Control Strategy
Critical process parameter (CPP)
Critical quality attribute (CQA)
Design Space
Knowledge Management
Lifecycle
Ongoing Process Verification (also known as continued process verification)
Product realisation
Quality by design
State of control
Traditional Approach
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Conclusion:
The draft guide has been brought in line with updates to ICH Q8-Q11 and the lifecycle
approach, as well as current trends in pharmaceutical manufacturing. There are a
number of significant changes in terms of how equipment, facilities and systems can
be planned and qualified, and how processes can be validated.
It is also no longer acceptable to have three consecutive batches to demonstrate that
the cleaning process is validated-a risk assessment is required to justify the number
required.
Included is guidance on the Verification of Transportation as well as separate sections
on Validation of Packaging, Utilities and Test Methods.
The document is currently available for public consultation with the deadline for
comments set for May 2014. The draft is subject to change and it may need further
clarity on a number of sections as highlighted above to avoid confusion including CPV,
ongoing process verification and deviations. It is expected that the new version will be
adopted be the European Commission in October 2014.
prohibited.
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References
Concept Paper on revision of Annex 15 of the GMP guide (EMA/INS/GMP/705397/2012),
European Medicines Agency, November 2012.
EudraLex - Volume 4 Good Manufacturing Practice (GMP) Guidelines, Annex 15
Qualification and Validation, 2001.
ASTM E2500-7 Standard Guide for Specification, Design, and Verification of
Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment, June
2007.
EudraLex - Volume 4 Good Manufacturing Practice (GMP) Guidelines, Annex 15
Qualification and Validation, 2014 draft.
International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline, ICH
Q8 Pharmaceutical Development, 2009.
Q9 Quality Risk Management, 2005.
Q10 Pharmaceutical Quality System, 2008.
Q11 Development and Manufacture of Drug Substances, 2012.
EudraLex - Volume 4 Good Manufacturing Practice (GMP) Guidelines, EU Annex 11
Computerised Systems, 2011.
Guideline on Process Validation (draft), European Medicines Agency, 2012.
ASTM E2500-7 Standard Guide for Specification, Design, and Verification of
Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment, June
2007.
PIC/S Recommendations on Validation Master Plan, Installation and Operational
Qualification, Non-sterile Process Validation and Cleaning Validation, PI 006-3, 2007
prohibited.
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About PharmOut
PharmOut is a professional consultancy offering product registration, engineering,
validation and regulatory compliance solutions to the Medical Device, Pharmaceutical
and Veterinary drug manufacturing industry from concept development, feasibility
studies, scale up, engineering design, project management to the final product
regulatory approval and GMP compliance certification.
How PharmOut can help

We offer the following range of services:
ISO, GMP & APVMA compliance consulting

Policies, SOP, and Forms. We can also help you obtain approval from the following
international regulatory authorities (APVMA, FDA, MHRA, and TGA).
Engineering
Our experienced industry engineers can develop concept and detailed designs, around
your production process ensuring full GMP compliance by careful project management
and verification (validation) to ensure that the exacting GEP standards are met.
GMP Compliance
We can visit your site before or after a FDA or TGA GMP audit to assess and improve
your quality management systems and/or validation documentation, business
processes and physical operations.
Quality Management Systems

We can help you create a Quality Management System from scratch, or bring your
current system into compliance.
Technical Document Writing

We can help you write procedures and work instructions that your staff will actually
use and can follow.
ISO & GMP consulting

We can provide practical recommendations and advice on the implementation of ISO
9001 for Pharmaceuticals or ISO 13485 for Medical Device Quality Management
Systems, Policies, SOP, and Forms. We can also help you obtain approval from the
following international regulatory authorities (FDA, MHRA, and TGA). This includes
Part 11 and Annex 11 compliance to FDA and TGA requirements.
Training
We run on-site or in-the-city classroom training on GLP, GMP compliance, validation
and documentation writing. We also develop e-learning modules on topics such as
Good Record Keeping that you can use for your ongoing training needs.
Validation
Our validation engineers / specialists can write validation plans, specifications and
qualification protocols for i.e. cleaning validation, equipment validation, computers
systems validation, analytical method validation or process validation.
prohibited.
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Who is affected by the changes?

What are the key changes in the new guidance?

Figure 1: ICH Q8, Q9, Q10 & Q11.

Cross-reference made to Annex 11 Computerised systems

Planning and documentation for Qualification &

Third Party Documents

Handling Changes and Deviations

The Approval Process

Qualification stages for equipment, facilities and

user requirements specification or initial process development through to the end of

User Requirements Specification (URS)

systems or equipment should be defined in a URS and/or a functional specification"

Design qualification (DQ)

Design reviewsplanned and systematic reviews of specifications, design, and design

Factory acceptance testing (FAT) /Site acceptance testing (SAT)

Installation qualification (IQ)

Operational qualification (OQ)

Performance qualification (PQ)

Figure 3: Process Validation approaches from the Draft Annex 15.

A lifecycle approach is applied linking product and

Traditional approach to validation

Continuous Process Verification

Ongoing Process Verification during Lifecycle

based on a toxicological evaluation to determine the product specific permitted daily

Typically, the cleaning procedure should be performed

Validation of Test Methods

Other notable changes within the Annex:

How PharmOut can help

ISO, GMP & APVMA compliance consulting

Quality Management Systems

Technical Document Writing

ISO & GMP consulting

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